O60609 (GFRA3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
GDNF family receptor alpha-3
Short name=GDNF receptor alpha-3
Short name=GDNFR-alpha-3
Short name=GFR-alpha-3

Gene names

Name:	GFRA3
ORF Names:	UNQ339/PRO538/PRO3664

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	400 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Receptor for the glial cell line-derived neurotrophic factor, ARTN (artemin). Mediates the artemin-induced autophosphorylation and activation of the RET receptor tyrosine kinase. Ref.7
Subcellular location	Cell membrane; Lipid-anchor › GPI-anchor.
Tissue specificity	Widely expressed in adult and fetus which exhibit a similar pattern. Essentially not expressed in the central nervous system, but highly expressed in several sensory and sympathetic ganglia of the peripheral nervous system. Moderate expression in many non-neuronal tissues, particularly those of the digestive and urogenital systems, but high expression in stomach and appendix. Several types of glandular tissues show low expression. Very low or no expression detected in the hematopoietic system. Ref.1
Post-translational modification	N-glycosylated. Ref.8
Sequence similarities	Belongs to the GDNFR family.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Coding sequence diversity	Alternative splicing
Domain	Signal
Molecular function	Receptor
PTM	GPI-anchor Glycoprotein Lipoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	neuron migration Inferred from electronic annotation. Source: Compara peripheral nervous system development Traceable author statement Ref.1. Source: ProtInc signal transduction Traceable author statement PubMed 9490034Ref.1. Source: ProtInc sympathetic nervous system development Inferred from electronic annotation. Source: Compara
Cellular_component	anchored to membrane Inferred from electronic annotation. Source: UniProtKB-KW cytoplasm Inferred from direct assay. Source: HPA external side of plasma membrane Inferred from electronic annotation. Source: Compara extrinsic to membrane Traceable author statement PubMed 9490034. Source: ProtInc intracellular membrane-bounded organelle Inferred from direct assay. Source: HPA plasma membrane Inferred from direct assay. Source: HPA
Molecular_function	axon guidance receptor activity Inferred from electronic annotation. Source: Compara receptor binding Traceable author statement PubMed 9407096. Source: ProtInc
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: O60609-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: O60609-2)

The sequence of this isoform differs from the canonical sequence as follows:
     127-157: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 31

31

Ref.6

Chain

32 – 374

343

GDNF family receptor alpha-3

PRO_0000010789

Propeptide

375 – 400

26

Removed in mature form Potential

PRO_0000010790

Amino acid modifications

Lipidation

374

1

GPI-anchor amidated asparagine Potential

Glycosylation

95

1

N-linked (GlcNAc...) Potential

Glycosylation

148

1

N-linked (GlcNAc...) Potential

Glycosylation

309

1

N-linked (GlcNAc...) Ref.8

Natural variations

Alternative sequence

127 – 157

31

Missing in isoform 2.

VSP_010942

Experimental info

Sequence conflict

108

1

K → R in AAC24355. Ref.1

Secondary structure

1

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400

Helix Strand Turn

Details...

Helix

161 – 170

10

Helix

173 – 185

13

Turn

188 – 190

3

Helix

193 – 206

14

Helix

209 – 216

8

Helix

225 – 233

9

Helix

237 – 240

4

Helix

248 – 256

9

Helix

259 – 271

13

Beta strand

274 – 276

3

Beta strand

281 – 283

3

Helix

285 – 293

9

Turn

294 – 297

4

Beta strand

302 – 304

3

Beta strand

307 – 309

3

Beta strand

312 – 315

4

Helix

322 – 324

3

Helix

325 – 336

12

Helix

339 – 355

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified July 19, 2004. Version 2. Checksum: B0BC252FE1F072C7	FASTA	400	44,511
	10 20 30 40 50 60 MVRPLNPRPL PPVVLMLLLL LPPSPLPLAA GDPLPTESRL MNSCLQARRK CQADPTCSAA 70 80 90 100 110 120 YHHLDSCTSS ISTPLPSEEP SVPADCLEAA QQLRNSSLIG CMCHRRMKNQ VACLDIYWTV 130 140 150 160 170 180 HRARSLGNYE LDVSPYEDTV TSKPWKMNLS KLNMLKPDSD LCLKFAMLCT LNDKCDRLRK 190 200 210 220 230 240 AYGEACSGPH CQRHVCLRQL LTFFEKAAEP HAQGLLLCPC APNDRGCGER RRNTIAPNCA 250 260 270 280 290 300 LPPVAPNCLE LRRLCFSDPL CRSRLVDFQT HCHPMDILGT CATEQSRCLR AYLGLIGTAM 310 320 330 340 350 360 TPNFVSNVNT SVALSCTCRG SGNLQEECEM LEGFFSHNPC LTEAIAAKMR FHSQLFSQDW 370 380 390 400 PHPTFAVMAH QNENPAVRPQ PWVPSLFSCT LPLILLLSLW
	Isoform 2 [UniParc]. Checksum: 43DEAB2E6B900CE3	FASTA	369	40,930
	10 20 30 40 50 60 MVRPLNPRPL PPVVLMLLLL LPPSPLPLAA GDPLPTESRL MNSCLQARRK CQADPTCSAA 70 80 90 100 110 120 YHHLDSCTSS ISTPLPSEEP SVPADCLEAA QQLRNSSLIG CMCHRRMKNQ VACLDIYWTV 130 140 150 160 170 180 HRARSLDSDL CLKFAMLCTL NDKCDRLRKA YGEACSGPHC QRHVCLRQLL TFFEKAAEPH 190 200 210 220 230 240 AQGLLLCPCA PNDRGCGERR RNTIAPNCAL PPVAPNCLEL RRLCFSDPLC RSRLVDFQTH 250 260 270 280 290 300 CHPMDILGTC ATEQSRCLRA YLGLIGTAMT PNFVSNVNTS VALSCTCRGS GNLQEECEML 310 320 330 340 350 360 EGFFSHNPCL TEAIAAKMRF HSQLFSQDWP HPTFAVMAHQ NENPAVRPQP WVPSLFSCTL PLILLLSLW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"GFRalpha3 is an orphan member of the GDNF/neurturin/persephin receptor family." Baloh R.H., Gorodinsky A., Golden J.P., Tansey M.G., Keck C.L., Popescu N.C., Johnson E.M. Jr., Milbrandt J. Proc. Natl. Acad. Sci. U.S.A. 95:5801-5806(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), TISSUE SPECIFICITY.
[2]	"The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment." Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J., Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P., Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E. , Heldens S., Huang A., Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D., Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L., Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C., Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J., Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M. Genome Res. 13:2265-2270(2003) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Lung and Substantia nigra.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Pancreas.
[6]	"Signal peptide prediction based on analysis of experimentally verified cleavage sites." Zhang Z., Henzel W.J. Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 32-46.
[7]	"Artemin, a novel member of the GDNF ligand family, supports peripheral and central neurons and signals through the GFRalpha3-RET receptor complex." Baloh R.H., Tansey M.G., Lampe P.A., Fahrner T.J., Enomoto H., Simburger K.S., Leitner M.L., Araki T., Johnson E.M. Jr., Milbrandt J. Neuron 21:1291-1302(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[8]	"Structure of artemin complexed with its receptor GFRalpha3: convergent recognition of glial cell line-derived neurotrophic factors." Wang X., Baloh R.H., Milbrandt J., Garcia K.C. Structure 14:1083-1092(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.92 ANGSTROMS) OF 151-363 IN COMPLEX WITH ARTN, GLYCOSYLATION AT ASN-309.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF051767 mRNA. Translation: AAC24355.1.
AY358997 mRNA. Translation: AAQ89356.1.
AY359037 mRNA. Translation: AAQ89396.1.
AK297693 mRNA. Translation: BAG60051.1.
AK314022 mRNA. Translation: BAG36733.1.
CH471062 Genomic DNA. Translation: EAW62152.1.
CH471062 Genomic DNA. Translation: EAW62153.1.
BC037951 mRNA. Translation: AAH37951.1.

IPI

IPI00445716.
IPI00445717.

RefSeq

NP_001487.2. NM_001496.3.

UniGene

Hs.58042.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2GH0	X-ray	1.92	A/B	151-363	[»]

ProteinModelPortal

O60609.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29114N.

STRING

9606.ENSP00000274721.

PTM databases

PhosphoSite

O60609.

Proteomic databases

PaxDb

O60609.

PRIDE

O60609.

Protocols and materials databases

DNASU

2676.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274721; ENSP00000274721; ENSG00000146013.
ENST00000378362; ENSP00000367613; ENSG00000146013.

GeneID

2676.

KEGG

hsa:2676.

UCSC

uc003lcn.3. human.
uc003lco.3. human.

Organism-specific databases

CTD

2676.

GeneCards

GC05M137588.

HGNC

HGNC:4245. GFRA3.

HPA

HPA020731.

MIM

605710. gene.

neXtProt

NX_O60609.

PharmGKB

PA28655.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG83952.

HOGENOM

HOG000059598.

HOVERGEN

HBG051726.

InParanoid

O60609.

OMA

QLFSQDW.

OrthoDB

EOG45X7W7.

PhylomeDB

O60609.

Gene expression databases

Bgee

O60609.

CleanEx

HS_GFRA3.

Genevestigator

O60609.

GermOnline

ENSG00000146013. Homo sapiens.

Family and domain databases

InterPro

IPR016017. GDNF/GAS1.
IPR003438. GDNF_rcpt.
IPR003505. GDNF_rcpt_A3.
[Graphical view]

Pfam

PF02351. GDNF. 3 hits.
[Graphical view]

PRINTS

PR01319. GDNFRALPHA3.
PR01316. GDNFRECEPTOR.

SMART

SM00907. GDNF. 3 hits.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

O60609.

GenomeRNAi

2676.

NextBio

10566.

SOURCE

Search...

Entry information

Entry name

GFRA3_HUMAN

Accession

Primary (citable) accession number: O60609
Secondary accession number(s): B2RA36 , B4DMY9, Q6UW20, Q8IUZ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 11, 2001
Last sequence update:	July 19, 2004
Last modified:	May 1, 2013
This is version 110 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.